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Resveratrol mitigates TOCP-induced spinal cord neurotoxicity by suppressing ferroptosis, a process mediated through
Sangping Li1, Shule Tan1, Xiangsheng Tian1
1Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, University of South China, Hengyang 421001, China.
Abstract:
This study investigated the protective effects of resveratrol (Res) against tri-o-cresyl phosphate (TOCP)-induced spinal cord neurotoxicity in adult hens, focusing on its modulation of ferroptosis via the p62/Keap1/Nrf2 pathway. Resveratrol is a classical neuroprotective compound with antioxidant properties and the ability to activate Nrf2. Adult hens were assigned to six groups: Control, TOCP, Ferrostatin-1 (Fer-1), Ferrostatin-1 + TOCP, Resveratrol, and Resveratrol + TOCP. Spinal cord tissues were analyzed using behavioral OPIDN scoring, histology (hematoxylin-eosin and Nissl staining), biochemical assays, and Western blotting for ferroptosis- and p62/Keap1/Nrf2-related proteins. TOCP exposure induced severe ultrastructural damage, including myelin sheath disruption and neuronal degeneration, along with increased malondialdehyde (MDA) and Fe2+ levels and decreased glutathione (GSH) and superoxide dismutase (SOD) activity. Western blot analysis demonstrated upregulation of NCOA4, ACSL4, Nrf2, P62, and LC3 II, with downregulation of GPX4, SLC7A11, FTH1, and Keap1. Resveratrol treatment significantly attenuated these molecular, biochemical, and histopathological alterations, mitigating oxidative stress and ferroptotic changes.
